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Nat Commun ; 11(1): 1703, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32245977


Optogenetic therapies for vision restoration aim to confer intrinsic light sensitivity to retinal ganglion cells when photoreceptors have degenerated and light sensitivity has been irreversibly lost. We combine adaptive optics ophthalmoscopy with calcium imaging to optically record optogenetically restored retinal ganglion cell activity in the fovea of the living primate. Recording from the intact eye of a living animal, we compare the patterns of activity evoked by the optogenetic actuator ChrimsonR with natural photoreceptor mediated stimulation in the same retinal ganglion cells. Optogenetic responses are recorded more than one year following administration of the therapy and two weeks after acute loss of photoreceptor input in the living animal. This in vivo imaging approach could be paired with any therapy to minimize the number of primates required to evaluate restored activity on the retinal level, while maximizing translational benefit by using an appropriate pre-clinical model of the human visual system.

Ceguera/terapia , Optogenética/métodos , Células Fotorreceptoras de Vertebrados/patología , Degeneración Retiniana/terapia , Células Ganglionares de la Retina/fisiología , Animales , Ceguera/diagnóstico , Ceguera/etiología , Modelos Animales de Enfermedad , Femenino , Fóvea Central/citología , Fóvea Central/diagnóstico por imagen , Fóvea Central/patología , Vectores Genéticos/administración & dosificación , Vectores Genéticos/genética , Humanos , Macaca fascicularis , Masculino , Oftalmoscopía , Imagen Óptica , Parvovirinae/genética , Degeneración Retiniana/complicaciones , Degeneración Retiniana/diagnóstico por imagen , Degeneración Retiniana/patología
Biomed Opt Express ; 4(11): 2527-39, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24298413


Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgan's method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm(2), which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health.

Opt Express ; 20(14): 14906-20, 2012 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-22772185


A distortion mapping and computational image unwarping method based on a network interpolation that uses radial basis functions is presented. The method is applied to correct distortion in an off-axis head-worn display (HWD) presenting up to 23% highly asymmetric distortion over a 27°x21° field of view. A 10(-5) mm absolute error of the mapping function over the field of view was achieved. The unwarping efficacy was assessed using the image-rendering feature of optical design software. Correlation coefficients between unwarped images seen through the HWD and the original images, as well as edge superimposition results, are presented. In an experiment, images are prewarped using radial basis functions for a recently built, off-axis HWD with a 20° diagonal field of view in a 4:3 ratio. Real-time video is generated by a custom application with 2 ms added latency and is demonstrated.